title: Elevated cholesterol precursors other than cholestanol can also be a hallmark for CTX.
abstract: Cerebrotendinous xanthomatosis (CTX) is an inborn error of bile acid synthesis in which hepatic conversion of cholesterol to cholic and chenodeoxycholic acids is impaired. Patients have abnormal bile alcohols in urine, normal to increased plasma cholesterol concentrations and increased concentrations of plasma cholestanol. Little is known about cholesterol precursors in CTX, however. We studied cholesterol and phytosterol profiles in two siblings with CTX during follow-up. While cholesterol concentrations were low in both patients, plasma cholestanol was 6-fold higher compared to control values. In addition, both siblings had a more than 100-fold increase in 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC). Lathosterol, lanosterol and sitosterol were increased in both patients while concentrations of desmosterol and campesterol were normal. In addition, plasma lathosterol/cholesterol ratios were significantly elevated. After treatment with chenodeoxycholate, both patients showed a marked decrease in cholestanol, 7DHC, 8DHC, lathosterol, lanosterol and sitosterol. In addition, the lathosterol/cholesterol ratio normalized, indicating that overall cholesterol synthesis was sufficiently suppressed. This study shows that elevated cholesterol precursors, other than cholestanol, can be a hallmark for CTX.
authors.affiliation: Department of Metabolic and Endocrine Diseases, University Medical Centre Utrecht, HP KC 02.069.1, Lundlaan 6 3584 CX, Utrecht, The Netherlands. M.G.deSain@umcutrecht.nl
authors.forename: M G M
authors.initials: MG
authors.lastname: de Sain-van der Velden
authors.forename: A
authors.initials: A
authors.lastname: Verrips
authors.forename: B H C M T
authors.initials: BH
authors.lastname: Prinsen
authors.forename: M
authors.initials: M
authors.lastname: de Barse
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: G
authors.initials: G
authors.lastname: Visser
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002775:Cholestadienols / Q000097:blood; D004083:Cholestanol / Q000097:blood*; D002784:Cholesterol / Q000097:blood*; D003684:Dehydrocholesterols / Q000097:blood; D006801:Humans; D007810:Lanosterol / Q000097:blood; D008297:Male; D011237:Predictive Value of Tests; D012855:Sitosterols / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D019294:Xanthomatosis, Cerebrotendinous / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000652:urine
chemical_list: D015415:Biomarkers; D002775:Cholestadienols; D003684:Dehydrocholesterols; D012855:Sitosterols; D002635:Chenodeoxycholic Acid; D007810:Lanosterol; C025473:gamma-sitosterol; C026359:cholesta-5,8-dien-3 beta-ol; C001521:lathosterol; D004083:Cholestanol; D002784:Cholesterol; C016705:7-dehydrocholesterol